ORIGINAL INVESTIGATIONS
Purpose of the study. Determine the value of genetic variants of a single nucleotide polymorphic site rs3736309 of intron 3 of aquaporin5 (AQP5) gene in the course of critical illness in patients with documented pulmonary infection. Materials and methods. Patients with critical illness admitted to the intensive care units were examined during the course of treatment (n=86, age 27 to 82 years, mean age 53.20±14.34 years). Main diagnosis included malignancies (15%), peritonitis (16%) and necrotizing pancreatitis (37%). Patients developed nosocomial pneumonia (55%), acute respiratory distress syndrome (ARDS) (54%), septic shock (48%), ARDS combined with septic shock (33%). Bacterial species of Pseudomonas aeruginosa , Klebsiella pneumoniae, Acinetobacter baumannii, and/or Proteus mirabilis alone or in association were revealed in lavage fluid. DNA genotyping DNA was carried out using tetraprimer polymerase chain reaction (PCR). Statistical processing was performed using GraphPad InStat program (GraphPad, USA).
Results. The distribution of frequencies of genotypes AA, GA and GG (AQP5, rs3736309) in cohort of patients corresponded to HardyWeinberg equilibrium (P=0.923) and was similar to frequencies of same alleles determined in a conditionally healthy Caucasian individuals (literature data) (P>0.05). In a subgroup of patients with septic shock and AQP5 AA (rs3736309) genotype the lower EVLWI values were found compared to patients with genotypes GG and GA with septic shock in spite of the same approach to treatment. The differences between genetically different subgroups of patients with septic shock were maintained throughout the life of the survey (P<0.05,days 1, 3, 5 and 7). Genetic variant AQP5 G+ (rs3736309) contributed to the development of pulmonary edema resistant to treatment (odds ratio, OR = 6,75; P=0.032). Only the subgroup of patients with septic shock and genotype G + (but not all patients or the subgroup of patients without septic shock of the same genotype) were characterized by significantly elevated levels of surfactant protein SPD in plasma compared to patients of genotype AQP5 AA with septic shock (P<0.05).
Conclusion. In septic shock, the presence of homozygous variant allele A (AA) of AQP5 rs3736309 is a favorable factor for patients developing the pulmonary edema. The presence of allele AQP5 G (rs3736309) is a risk factor for developing severe pulmonary edema and unfavorable prognosis in spite of treatment.
The aim of the study was to determine the correlation between blood levels of Nterminal portion of the inactive precursor of natriuretic peptide of Btype (NTproBNP) and hemodynamic, clinical and laboratory parameters in the course of intensive treatment of patients with severe communityacquired pneumonia (CAP).
Materials and methods. The study included 12 patients (10 men and 2 women) with severe CAP, age 25—88 (51.5 (41.25; 69)) years. The severity of the condition was as follows (averages and percentiles): on a scale of CURB65 — 3—5 (4; 4,5) scores, APACHE II — 16—33 (23 (18.75; 25)) scores, SOFA — 6—16 (10 (9; 12.75)) points. Concentartions of NTproBNP in venous blood 24—36 h post admission and on day 5 of treatment were determined by analyzer Dimension Xpand Plus (Siemens).
Results. Within 24—36 hours after the admission concentration of NTproBNP was 783.5 (460.75; 4150.25) pg/ml. The content of the biomarker remained higher than in norm in 66.7% of patients. By the 5th day the concentration of the biomarker was 537 (376.25, 1334) pg/ml. In surviving patients (66.7%), the concentration of NT proBNP was decreasing (P=0.008) to day 5 of treatment from 918 (560, 8501) to 391 (341, 1010) pg/ml. CAP patients who did not survived later (32.3%) exhibited no decrease of the biomarker concentration. Significant correlation between NTproBNP on admission to ISU and index of total peripheral vascular resistance on day 2 of intensive treatment (r=0.63; p<0.05) and day 5 (r=0.58, P<0.05) was revealed. Echocardiography systolic pulmonary artery pressure correlated with the content of NTproBNP 24—36 hours after admission to the Intensive Care Unit and on the 5th day of treatment.
Conclusion. We suggested that the reason for increased concentration of NTproBNP is an overload of the right ventricle myocardium due to pulmonary hypertension as a characteristic of acute respiratory distress syndrome.
FUNDAMENTALS OF ANESTHESIOLOGY AND REANIMATOLOGY
Congestive heart failure is consistently associated with adverse outcomes, and is characterized by a twofold increase in mortality in noncardiac surgery. In this regard, developing the methods aimed to prevent and treatacute heart failure (AHF) in the intraoperative period remain a challenging problem.
Objective. To evaluate the efficacy of preoperative levosimendan infusion in reduction both mortality and duration of treatment of elderly patients with reduced left ventricular ejection fraction in noncardiac surgery.
Material and Methods. Design: Multicenter blind randomized placebocontrolled study. Patients: 81 patients operated on abdominal organs. The main endpoint of the study: The length of stay in the Intensive Care Unit (ICU) and at the hospital were chosen as the primary endpoints. The secondary endpoints of the study were 30 day and annual mortality, the rate of acute myocardial infarction and stroke.
Results. Levosimendan infusion at a rate of 0,05 μg/kg/min — 0,1 μg/kg/min to patients with low left ven tricular ejection fraction just before the surgery reduced the length of stay in ICU for 2 days and required hospital stay for 3 days. NTproBNP showed the best ratio of sensitivity/specificity in predicting 30day mortality in cumulative group: AUC=0,86 (90,77 to 0,93), P<0,0001. From other indicators the most informative were the Inotropes scoring, no change or decrease of a left ventricular ejection fraction, and cardiac index.
Conclusion. To reduce perioperative mortality, the intravenous infusion of levosimendan at a rate of 0,05—0,1 μg/kg/min in elderly patients with low left ventricular ejection fraction is recommened as a preoperative preparation the day before the alleged noncardiac surgery.
Chronicle
FOR PRACTIONER
Goal of study: to improve hemodynamics, respiratory exchange and metabolism of potential donor organs by using combination of Lthyroxin, triiodothyronine, methylprednisolone, desmopressin acetate and insulin.
Material and Methods: The clinical study included 98 potential donors (PD) with confirmed diagnosis of brain death. Braindead PD were divided into two groups: the 1st group included 43 PD with traumatic brain injury; the 2nd group included 55 PD with a stroke. PD from the 1st and 2nd groups were divided into two subgroups: main subgroup (n=18 and n=30) included those who received Lthyroxine, triiodothyronine and dessom pressin orally; control subgroup (n=25 and n=25) included those who did not receive these drugs. Hemodynamics, electrolytes, biochemical parameters, respiratory exchange and free triiodothyronine and thyroxine in blood were determined during the study.
Results and discussion: In the course of the intensive therapy in control subgroups of both groups of PD the doses of noradrenalin and dopamine were not changed. However, the doses of noradrenalin and dopamine were decreased significantly in main subgroups of both groups during the course of the hormone therapy. There were no significant changes in hemodynamics in PD from both control subgroups, whereas in main groups hemodynamics parameters were decreased due to hormone therapy. Significant changes of blood pressure were observed in the main subgroups. Despite exogenous administration, in the main subgroups T3 remained at the lower limit of norm, whereas T4 increased. Improved hemodynamics and gas exchange were revealed in PD following hormone therapy that was important for the blood flow in organs. Following transplantation, in recipients of organs from control subgroup of PD the rejections of the transplants were significantly more frequent than rejections of organs from PD which comprized the main subgroup receiving hormones.
Conclusion. Hormone administration to braindead PD with confirmed brain death led to significantly reduced doses of noradrenalin and dopamine and improved hemodynamics and gas exchange parameters. Oral administration of thyroid and hypophisis hormones to PD with confirmed brain death seems feasible.
Regional citrate anticoagulation (RCA) is an increasingly common technique at continuous renal replacement therapy in critically ill patients with acute kidney injury (AKI). Regardless of the new anticoagulation protocols of RCA, citrate accumulation is remaining infrequent but unfavorable complication with poor outcome. Traditional treatment of this complication includes interruption of citrate administration, as well as increasing the
flow of blood and dialysate.
Objective: to evaluate safety and effects of a new modality, the continuous «calciumfree» hemodiafiltration, on electrolyte and acidbase status in a patient undergoing cardiac surgery with citrate accumulation after RCACRRT.
Materials and metods. Reduced level of calcium in the extracorporeal circuit has been achieved by applying calciumfree CiCa Dialysate K4 solution for predilution and dialysate. To prevent hypophosphatemia and hypomagne semia 500 ml/h Multiplus K+ solution was administered in a postdilution mode. Desired level (0.91.2 mmol/L) of ionized calcium was achieved by continuous infusion of 5% calcium chloride 612 ml/h into a separate central vein line.
Results. Although the target level (0.5mmol/l) of calcium after hemofilter was achieved only after 16 hours, the lifespan of the extracorporeal circuit was 23.5 hours. Total serum calcium decreased from 3.27 to 1.98 mmol/L. Other markers of acidbase balance had been fully normalized.
Conclusion. «Calciumfree» hemodiafiltration might be a promising treatment option for a citrate accumulation syndrome that ensures citrate removal and establishes satisfactory anticoagulation.
17yearold patient with hypervolemia of lesser (pulmonary) circulation was operated for tetralogy of Fallout with pulmonary atresia. She was successfully treated by intensive therapy using techniques of noninvasive ventilation with regard to clinical status of hypovolemia of the lesser (pulmonary) circulatory system in the early post operative period.
CRITICAL ILLNESS IN NEWBORNS
Purpose. With the aid of indirect calorimetry, to evaluate whether the nosological factors affect energy exchange in severely ill newborns.
Materials and methods. Indirect calorimetry was employed to determine the true energy expenditure in new borns under the mechanical ventilation because of intranatal postanoxia encephalopathy (n=19), severe sepsis (n=18), and urgent surgery (n=19). Energy expenditure at rest was estimated at the beginning of intensive therapy and in in 48 hours. Sedation in groups was similar.
Results. At the first stage, the energy exchange in all newborns was characterized by hypometabolism. In cases of damage of the central nervous system the anaerobic metabolism was increased, and the principal used substrate was glucose; the most prolonged hypometabolism was revealed in newborns with sepsis, in which the utilization of lactate was decreased, and the main energetic substrate were lipids; in early postoperative period, the decrease in energy expenditure was not associated with preferential oxidation of glucose or lipids, and disappeared due to elimination of anesthetics.
Conclusion. Energetic hypometabolism can be considered as a main reaction of the newborn organism to previous invasion. Acute posthypoxic brain damage in newborns is characterized by high activity of peroxidation associated with hypometabolism. For newborns with severe sepsis a slow recovery of aerobic metabolism and intensity of energy expenditure were evident. Early postoperative period in newborns was characterized by profound iatrogenic hypometabolism with fast normalization of energy expenditure.
INJURY
Aim of investigation. To prove the usefulness of the use of embryonic fibroblasts for the regeneration of cartilaginous tissue.
Material and methods. New experimental model of symphysis pubis rupture followed by its recovery was employed in 24 male Shinshilla rabbits (2.3—3.5 kg body mass) in 3 series of experiments. In the first series, reconstruction was not employed. In the 2nd series, the reconstruction of symphisis was performed with the aid of tantal wired cerclage (d=1.2 mm). In the 3d series, the reconstitution was the same as in the previous series of experiments with addition of grown embrional allofibroblast tissue pieces. Duration of experiments was 7, 14, 21and 30 days. After each experiment, pieces of cartilaginous tissue were fixed with 10% neutral formalin and embedded in paraffin. Histological sections were stained with hematoxylin, eosin and VanGieson.
Results. After the rupture of symphysis pubis of the pelvic bone, the cartilaginous tissue undergone alterations followed by formation of chondromatous nodules of different sizes and sclerosis of surrounding muscular and osseous tissues. In the second series of experiment after pelvis symphysis pubis rupture and symphysis recovery with the help of cerclage, the morphologic investigation revealed the formation of mixed initial callus consisting of connective and chondromatous tissue elements. In the third series of experiment it has been shown that within 4 weeks of experiment, the connective tissue with intensive basophil stain is formed in the area of symphysis pubisrupture. Connective tissue formation in surrounding soft tissue structures was associated with the formation of cartilaginous cells.
Conclusion. Process of formation of cartilaginous tissue in the area of symphysis pubis rupture as evident by the experimental observation demonstrates the stimulating influence of allogeneic fibroblasts on process of cartilaginous tissue regeneration that ensures premises for clinical development of suggested method of regeneration.
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